Biology subjects

Nakao, T.

Publications and source records attributed to Nakao, T..

3 recordsLinked to original sources

bioRxiv2026

Transcriptomic signatures associated with mania-to-depression and depression-to-mania transitions in bipolar disorder: a case report using induced microglia-like (iMG) cells

IntroductionBipolar disorder (BD) is characterized by recurring episodes of mania and depression. Despite extensive research, the pathophysiology underlying these mood swings remains elusive. Emerging evidence indicates a potential role for neuroinflammation and microglial activation in the pathophysiology of BD. MethodsWe employed a reverse-translational approach to generate directly induced microglia-like (iMG) cells from peripheral blood monocytes of a single patient with BD, repeatedly sampled across depressive, manic, and subsequent depressive phases. RNA sequencing was performed on iMG cells at each time point to identify differentially expressed genes related to mood state transitions. ResultsA thorough analysis of longitudinal gene expression data has led to the identification of three functional gene categories: "state-dependent genes", "depression-to-mania transition genes (named: firing genes)", and "mania-to-depression transition genes (named: extinguishing genes)". A total of 168 firing, 59 extinguishing, and 77 state-dependent genes were identified. Notably, functional annotation revealed that, compared to the extinction gene set, the firing gene set was enriched in immune and inflammatory response pathways, particularly early-response cytokines such as IL1B and TNF. ConclusionsBased on these findings, we propose that inflammatory immunomodulation by microglia contributes to mood switching in BD, especially in the process of depression-to-mania transition. The classification of genes by their relationship to state transitions offers a novel framework for understanding the molecular mechanisms underlying this complex disorder and may identify potential therapeutic targets to stabilize mood. Further validation with larger cohorts is warranted.

neuroscience↗

bioRxiv2023

Externally provided rewards increase internal preference, but not as much as preferred ones without extrinsic rewards

It is well known that preferences are formed through choices, known as choice-induced preference change (CIPC). However, whether value learned through externally provided rewards influences the preferences formed through CIPC remains unclear. To address this issue, we used tasks for decision-making guided by reward provided by the external environment (externally guided decision-making; EDM) and for decision-making guided by ones internal preference (internally guided decision-making; IDM). In the IDM task, we presented stimuli with learned value in the EDM and novel stimuli to examine whether the value in the EDM affects preferences. Stimuli reinforced by rewards given in the EDM were reflected in the IDMs initial preference and further increased through CIPC in the IDM. However, such stimuli were not as strongly preferred as the most preferred novel stimulus in the IDM, indicating the superiority of intrinsically learned values (SIV). The underlying process of this phenomenon is discussed in terms of the fundamental self-hypothesis. Author SummaryWe make decisions based on internal value criteria, which are individual preferences, or based on external value criteria, which are the values learned from the external environment. Although it is known that values are learned in both types of decisions, is there a difference in the nature of these values? Our study uses simulation and fits human behavioral data to address this question. The results showed that stimuli that were learned to be highly valued because of external feedback became preferred in subsequent preference judgments. However, it is interesting to note that such stimuli were not chosen as much as stimuli that were preferred without influence from the external environment. This finding suggests that values formed through ones own criteria have characteristics distinct from those formed through external environmental influence. Our findings promote an integrated understanding of the decision-making process.

animal behavior and cognition↗

bioRxiv2019

Clinical evaluation of presepsin considering renal function.

Presepsin, a glycoprotein produced during bacterial phagocytosis, has attracted attention as a sepsis marker for bacterial infections. However, since presepsin is affected by renal function, there is a need to separate the evaluation criteria for diagnosis of healthy subjects from that of patients with renal disorder. In this study, we analyzed the influence of kidney function on presepsin concentrations and recalculated the reference range based on the findings. For this purpose, EDTA-whole blood from 47 healthy subjects and 85 patients with chronic kidney disease was collected and used for presepsin measurement by PATHFAST. Presepsin was found to be significantly correlated with creatinine (r = 0.834), eGFRcreat (r = 0.837), cystatin-C (r = 0.845) and eGFRcys (r = 0.879).\n\nFurthermore, in patients with chronic kidney disease at different glomerular filtration rate stages, the presepsin levels showed a significant increasing trend with advancing glomerular filtration rate stage. The reference range, calculated by nonparametric method using a total of 67 cases of healthy volunteers and patients with chronic kidney disease G1, was found to be 59-153 pg/mL, which was notably lower than the standard reference range currently used. Presepsin concentrations were positively correlated with some biomarkers of renal function, indicating that it is necessary to consider the influence of renal function in patients with renal impairment. Further, the recalculated reference range might be more useful for diagnosis and treatment of sepsis than the standard reference currently in use, which likely includes false high values.

biochemistry↗